Investigations in this laboratory are directed toward development of knowledge of blood platelet function in normal hemostasis, of their role in the pathogenesis of inherited and acquired bleeding disorders, and their contribution to vascular injury, atherosclerosis and thrombotic disease. Transmission and scanning electron microscopy, cytochemistry, immunocytochemistry, biochemistry, physiology, cell sizing, and aggregometry are combined to facilitate the development of information. New concepts and technical approaches have resulted from our past work and will continue to develop from future efforts. The combination of solidly established methods and advanced technology will provide the basis for investigation into unsolved problems of platelet structural physiology and pathology. Patient problems remain of paramount interest. We have discovered the second case of the Gray platelet syndrome and will attempt to define the basis for defective platelet granule formation in this disorder. The pathogenesis of giant granule formation and a new crystalline inclusion we have discovered in platelets from patients with chronic myelogenous will be investigated. We have recently made advances in the technique of platelet sizing and will apply them to the survival of giant platelets. Work on platelet prostaglandin synthesis in normal and abnormal platelets is progressing rapidly and in our recent studies has been linked to cyclic GMP production. We have used the calcium ionophore, A23187, to demonstrate that a rise in cytoplasmic calcium is sufficient to trigger contraction in platelets and will use the agent to further characterize the platelet sarcoplasmic reticulum. The role of platelets in host defense was largely developed in this laboratory and in vivo studies of platelet-bacterial interaction are in progress. Investigations of cyclic AMP and cyclic GMP dependent protein kinases in normal and abnormal platelets have been started. This broad-based but carefully coordinated approach to platelet studies will provide new and important information on platelets in health and disease.